This invention relates to the use of danazol, a known material, in the treatment of hematologic disorders such as paroxysmal nocturnal hemoglobinuria and autoimmune hematologic disorders such as autoimmune hemolytic anemias, secondary immune thrombocytopenias and other blood, cytopenias, and in a method of restoring immune homeostasis in a patient requiring such therapy as well as selected immune deficiency syndromes.
Danazol, known chemically as 17.alpha.-Pregna-2,4-dien20-yno[2,3-d]isoxazol-17-ol; 17.alpha.-pregn-4-en-20-yno[2,3-d]isoxazol-17-ol; 1-ethynyl-2,3,3a,3b,4,5,10,10a,10b,11,12, 12a-dodecahydro-10a-12a-dimethyl-1H-cyclopenta[7,8]phenanthro[3,2-d]isoxaz ol-1-ol; or 17.alpha.-ethynyl-17.beta.-hydroxy-4-androsteno[2,3-d]isoxazole; and available as Danocrine from Winthrop Laboratories is a synthetic hormone derived from ethisterone. See British Pat. No. 905,844 (1962 to Sterling Drug), C.A. 58, 689c (1963); and U.S. Pat. No. 3,135,743 (1964 to Sterling Drug). Danazol has the formula: ##STR1##
Danazol is classified as an anterior pituitary suppressant and is an androgen which is often prescribed for the treatment of fibrocystic breast disease, endometriosis and hereditary angioedema. Danocrine.RTM. brand of danazol is available in 50, 100 and 200 mg. capsules. See Merck Index, 12th Edition, monograph 2799 (1983).
The treatment of idiopathic thrombocytopenic purpura (ITP) with danazol is reported by the present applicants and others in the June 9, 1983 edition of the New England Journal of Medicine 308:1396-1399 at an oral dosage rate of 200 mg. two to four times a day. ITP is an autoimmune disorder, most common in young women, in which platelets react with an auto-antibody and are destroyed by macrophages. There is no known underlying disease causing thrombocytopenia in ITP.
Prior methods of therapy for autoimmune disorders include the use of glucocorticoids, which have potentially serious side effects such as osteoporosis, infections, diabetes mellitus, complications often unavoidable over periods of prolonged use. The use of danazol or other androgens as a partial or complete replacement for glucocorticoids will minimize and in some cases prevent these serious side effects as well as reduce the amounts of glucocorticoids required for effective therapy.